What Are CGRP Monoclonal Antibodies?

CGRP (calcitonin gene-related peptide) monoclonal antibodies (MoAbs) prevent migraine. The approval of the first CGRP MoAbs in 2018 was a breakthrough in migraine treatment. They were the first migraine-specific preventive drugs. There are currently 4 approved CGRP MoAbs. CGRP MoAbs do not stop a migraine attack once it has started.^1,2

How are the trigeminal nerve and CGRP connected?

Migraine is a result of dysfunctional nerve signaling. Key players are the trigeminal nerves and CGRP, a signaling molecule. The trigeminal nerve runs from the brain to the face. It is responsible for facial and head sensations and jaw movement.¹

CGRP is a small protein that transmits signals in the brain. Sensory nerves produce and release CGRP. Drugs that block CGRP help prevent and treat migraine. Other names for this class of drugs are:¹

• CGRP MoAbs
• CGRP inhibitors
• CGRP antagonists

How do CGRP MoAbs work?

CGRP MoAbs disrupt the CGRP process. The lock-and-key analogy helps us understand how they do this. The CGRP protein is the key. The CGRP receptor is the lock. When the key opens the lock, the pain process begins or worsens. Drugs that block the lock or change the shape of the key interfere with the function of CGRP. So these drugs are useful treatments for migraine.^1,2

One CGRP MoAb blocks the "lock:"³

• Aimovig™ (erenumab-aooe)

Three other CGRP MoAbs attach to the "key":^4-6

• Ajovy™ (fremanezumab-vfrm)
• Emgality™ (galcanezumab-gnlm)
• Vyepti™ (eptinezumab-jjmr)

Do CGRP MoAbs work for episodic migraine?

In general, CGRP MoAbs prevent 3 or 4 migraine days per month for people with episodic migraine. This is an average – your results may be better or worse. For comparison, the beta-blockers and anticonvulsants approved for migraine prevent about 1 to 2 migraine days per month. Results from clinical trials of CGRP MoAbs found:^7-10

• 4.7 fewer migraine days per month with Emgality
• 3.9 fewer migraine days per month with Vyepti
• 3.7 fewer migraine days per month with Ajovy
• 3.2 fewer migraine days per month with Aimovig

Do CGRP MoAbs work for chronic migraine?

In general, CGRP MoAbs prevent 4 to 7 migraine days per month for people with chronic migraine. This is also an average. Results vary from person to person. Clinical trials showed these results:^11-14

• 7.6 fewer migraine days per month with Vyepti
• 6.6 fewer migraine days per month with Aimovig
• 5 fewer migraine days per month with Ajovy
• 4.6 fewer headache days per month with Emgality

How are Aimovig, Ajovy, Emgality, and Vyepti different?

The 4 CGRP MoAbs are taken on different schedules and in different ways.^3-6,15

• Aimovig and Emgality are given by injection once a month.
• Emgality requires a “loading dose,” which is the first dose of the drug. This is usually 2 injections to start, then a monthly injection after that.
• Ajovy is given by injection every 1 or 3 months.
• Vyepti is given as a 30-minute infusion once every 3 months. An infusion is when you get a treatment through a needle into your vein (intravenously or IV).

Each of these drugs works in a slightly different way. All are effective at preventing migraine and have similar side effects.^3-6

What are the possible side effects?

The side effects of CGRP MoAbs are generally mild or moderate. Redness or pain at the injection site is common. A small number of people had an allergic reaction to the drugs. Some people treated with Vyepti in clinical trials had an upper respiratory infection (cold).^3-6,11-14

Aimovig was linked to constipation and new or worsening high blood pressure. Doctors now monitor people taking Aimovig for rising blood pressure. You may need to take a different migraine drug if there is no other cause for your increasing blood pressure.
Side effects can vary depending on the specific drug taken.³

These are not all the possible side effects of CGRP MoAbs. Talk to your doctor about what to expect when taking CGRP MoAbs. You also should call your doctor if you have any changes that concern you when taking CGRP MoAbs.

How are gepants different?

As of March 2023, there are 4 CGRP gepants approved by the FDA, including:^16-19

• Nurtec™ ODT (rimegepant)
• Qulipta™ (atogepant)
• Ubrelvy™ (ubrogepant)
• Zavzpret™ (zavegepant)

Because the drug families have similar names, CGRP MoAbs and CGRP gepants are sometimes confused. Both MoAbs and gepants target CGRP. However, these drugs have different purposes. CGRP MoAbs prevent migraine. Some gepants (Nurtec ODT and Ubrelvy) are approved to prevent migraine. Qulipta and Zavzpret are acute treatments – they are taken at the start of an attack.^1,2,16-19

Also, CGRP moAbs are given by injection or IV. CGRP gepants are given by pill or nasal spray.^1,2

What are the 4 letters at the end of the scientific name?

Many drugs have 2 names. There is a brand name, such as Aimovig, Ajovy, Emgality, or Vyepti. There is also a scientific name, such as erenumab-aooe, fremanezumab-vfrm, galcanezumab-gnlm, or eptinezumab-jjmr.²⁰

You may have wondered about the 4 letters at the end of the scientific name. A deeper dive explains their purpose. The CGRP MoAbs are biologic drugs. Biologic drugs are proteins made from the cells of living organisms. They are much more complex than conventional drugs.²⁰

A biosimilar is very much like the original biologic. But it is not exactly alike. The FDA wanted the names to reflect this. So biologics and their biosimilars share a scientific name, but each has its own 4-letter suffix.²⁰

Before beginning any migraine treatment, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.